ADVANCED PSYCHOPHARMACOLOGY

Psychology 572                     	                              Spring, 2005
Dr. John M. Morgan                                        Tuesday & Thursday, 8am to 9:20
                                                                      Natural Resources 201

NICOTINE

	Tobacco has been used since the time of the Maya: the earliest 
reference to Tobacco is in a Mayan carving circa 300AD (Palfai & 
Jankiewicz, 1997).  Columbus was the first recorded westerner to be 
exposed to it in 1492 and, by the early 1500’s, sailors had returned to 
Europe with the “smoke stick” habit.  This started the love affair with 
tobacco worldwide.
	The word nicotine derives from the Latin name for tobacco, 
“nicotiana tabacum.”  The active ingredient was isolated in the 1820’s 
and named nicotine. With the advent of cigarettes in the 1850’s came 
mass popularity among adults and children.  So great was the habit 
among the populace that cigarettes were banned in fourteen states by 
1925.  Bans were repealed when it was realized that tax revenues 
were declining.  By World War II smoking had reemerged and become 
popular again.  Cigarettes were given free to servicemen to relax them 
and give them a social outlet during the stress of war (Jarvik, 2003).
	1938 was the year the first study came out linking smoking 
cigarettes with lung cancer and yet it was not until 1964 that the first 
warnings went out on packages.  In 1971 the warnings became 
statements of fact (“smoking may be” to “smoking is dangerous”).  In 
1986, Surgeon General C. Everett Koop presented evidence to support 
the hypothesis that nonsmokers inhaling secondhand smoke from 
smokers may be at risk of medical complications and cancer.  
	This background information is critical to understanding the 
relative short amount of time nicotine has been studied.  It has only 
been in the last eighty years that the harmful effects of the poison 
nicotine has been studied.  It is the most ingested poison and has no 
medicinal purpose (P&J, p.348).  It also has one of the lowest lethal 
dose ratings of 60 mg.  
	Murray E. Jarvik is one of the foremost researchers in nicotine 
use.  His work with the pharmacology of nicotine addiction led to the 
development of nicotine gum and the nicotine patch.  One of his early 
studies was trying to condition monkeys to smoke.  He would reward 
the monkey with a drink of water once they inhaled cigarette smoke.  
His hope was that the monkey would become conditioned to smoke 
even when the reward was not present.  This hypothesis turned out to 
not be true.  It is rare for any animal to voluntarily smoke long term as 
humans do.  He was able to show that smoking behaviour in monkeys 
could be inhibited by using hexamethonium, mecamylamine, 
scopolamine and amphetamine, each which target different nicotine 
receptors in the brain.  In 1970 he contributed a chapter to William 
Hunt’s book: Learning Mechanisms in Smoking.  His opinion made the 
connection between nicotine and tobacco addiction.  
       In the 1980’s Ellen Gritz and Vivian BaerWeiss showed that 
chewing tobacco causes nicotine to be absorbed into the bloodstream.  
They convinced members of the UCLA baseball team who were heavy 
tobacco chewers to give blood samples and compared the samples for 
nicotine.  This led to use of the nicotine patch for those who desire the 
effects of nicotine but not the damage of the smoke.  
       Relapse testing has been done to determine why only 20 percent 
of smokers are successful in quitting.  Sauth Shiffman set up a 
twentyfour hour phone hotline for smokers to call when they needed a 
cigarette.  He used it to determine what they were thinking when the 
cravings were frustrating them.
       In the late 1980’s a study determined when a person’s favourite 
cigarette of the day was and how average smokers differed from heavy 
smokers.  Average smokers most enjoyed a cigarette after a large 
meal while heavy smokers most enjoyed the first cigarette of the day.
       Surgeon General C. Everett Koop was the instrumental one in 
pushing tobacco control in public policy.  Since his Nicotine Addiction 
report of 1988, more money has been allocated and science has been 
done to change the public’s perception of tobacco use.  This 
educational method has had some success in changing tobacco usage 
among some segments of the population.  
       In the 1990’s, research was done to determine “if schizophrenic 
patients who smoked heavily might be helped with nicotine patches.”  
They found that it did reduce smoking in patients who were not 
motivated to stop smoking.  
       Recent research has been in the area of measuring smoking 
related changes in the brain.  The researchers at UCLA measured 
nicotine impact on the brain through MRI imaging and then compared 
them to cravings caused in volunteers who watched special videos of 
smoking.  They have found that the anterior cingulated and nucleus 
accumbens regions of the brain are active in these studies.  More 
research is happening in the area of cognitive changes in the brain 
functioning when smoking or abstaining from smoking.
       
       
       
       Henningfield, J. E. (2003).  E.Everett koop, M.D., Sc.D.: A 
visionary leader of science-based public health policy and tobacco 
control. Nicotine & Tobacco Research, 5, 611-612.
       
       Koop, C. E., (2003). Tobacco addiction: accomplishments and 
challenges in science, health and policy. Nicotine & Tobacco 
Research, 5, 613-619
       
       Jarvik, M. E., (2003).  My Career in Psychopharmacology. Nicotine 
& Tobacco Research, 5, 145-149.
       
       Palfai, T. & Jankeiewicz, H. (1997).  Drugs and Human Behavior, 
second edition.  Brown & Benchmark, PP344-348
	 
	
       Chemical Experience of Nicotine
       Jenna Devoid
       Nicotine is found in the leaves of the tobacco plant 
predominantly, but it is also found in the nightshade family of plants, 
including tomato, potato and green pepper, although not to the same 
degree as tobacco.  In plants it is an oily liquid (Wikipedia).  
       Nicotine is an agonist of acetylcholine (Ach), which is produced 
in the brain (“Mind”).  This means that nicotine mimics the chemical 
actions of acetylcholine (“Cholinergic”).  Nicotine’s chemical structure 
is a lot like acetylcholine with slight differences (“Cholinergic”). 
Nicotine is chemically formed by a pyridine ring connected to a 
pyrrolidine ring and can be superimposed to an acetylcholine structure 
(Novick). Nicotine will therefore trigger the same receptors and bring 
about similar actions and reactions as acetylcholine (“Cholinergic”). 
The chemical formula for nicotine is C10H14N2.  The  organic 
molecule weighs 162.23 g/mol, has a boiling point of 247 degrees and 
a melting point of  negative 7.9 degrees Celsius (Wikipedia). In people 
its LD50 is 40 to 60 mg (Wikipedia).
        Nicotine is also an alkaloid, meaning that it is a base 
(“Extracellular”).  However, it is a weak base, so it therefore requires a 
basic environment to pass through cell membranes; this is why 
cigarette companies often use an ammonia based chemical in 
cigarettes to facilitate this action (Novick).  Nicotine is a stimulant 
and a sedative , meaning that it both arouses and calms physiological 
activity (Dictionary.com).  
	Nicotine has different pathways for activating the body based 
upon method of consumption.  In the form of cigarettes, or inhalation, 
the amount taken is relatively small, with most of it being destroyed by 
the heat of the cigarette (Wikipedia).  It is then taken into the lungs 
where it is absorbed before entering the bloodstream.  The 
bloodstream transports nicotine to the brain through the heart, as well 
as other parts of the body (DiConsiglio). It takes seven seconds for 
nicotine to reach the lungs after ingestion.  Nicotine easily crosses the 
blood-brain barrier (Wikipedia). The amount of nicotine that is taken 
into the body is dependent upon the brand of cigarette (i.e.chemicals 
added such as the aforementioned ammonia) and how the cigarette is 
inhaled.  The nicotine concentration found in the body typically peaks 
in minutes before decreasing.  The half-life of nicotine in the body is 
about two hours (Novick).
       When sniffed or chewed (via gum or snuff), or taken orally, the 
nicotine enters the bloodstream through the mucus membranes of the 
mouth or nose depending on the ingestion method (DiConsiglio). 
Herein the level of nicotine in the body will reach its apex around 
thirty minutes and decrease over the next two hours (Novick).  
       Acetylcholine activates two types of receptors, muscarinic and 
nicotinic receptors.  In this case nicotine activates the cholinergic 
nicotinic receptors.  The nicotinic ion channel, or sodium channel, is 
composed of a transmembrane polypeptide, or protein.  When 
activated by nicotine its cation channel opens, as it would for 
acetylcholine, and allows positively charged sodium (Na+) and 
potassium (K+) ions to enter the cell.  This influx of positively charged 
ions depolarizes the postsynaptic membrane.  This may or may not 
meet the threshold requirements of the neuromuscular or nerve cell 
(“Cholinergic”).  If threshold is met than an excitatory synaptic 
response ensues, or action potential of that neuron.  
       The nicotinic receptors are located in the skeletal muscles, or 
the neuromuscular junction (Kimball).  They are also found as part of 
the parasympathetic nervous system on the post-ganglionic neurons, 
which are part of the autonomic nervous system, which controls 
involuntary actions of physiology (Kimball). The parasympathetic 
nervous system, as a part of the autonomic nervous system, is 
oriented towards stimulation of physiology.  The parasympathetic 
nervous system receptors affected by acetylcholine are involved in the 
body’s alertness, memory, respiration and movement of muscle 
(“Mind”).  When activated it will stimulate, or arouse, digestion, blood 
pressure and respiration.  This stimulation is the result of epinephrine 
being released by the adrenal glands activated by the nicotinic 
receptors. 
	Nicotine also affects the central nervous system.  In the brain 
cholinergic receptors responsible for addiction are affected.  This is a 
result of the release of dopamine into a part of the brain called the 
nucleus accumbens (“Mind”), which is found in the underside of the 
lateral ventricle in the brain (Dictionary.com).  
       The chronic use of nicotine causes an over abundance of 
dopamine (Novick). As a motivation or pleasure stimulant this creates 
a reinforcing effect. Nicotine has been found to increase the 
concentration of receptors for dopamine, enhancing its effects.  This 
is in addition to dopamine receptors becoming sensitized due to the 
increased release of glutmate (Novick).  A side effect of which is 
hyperglycemia which is an overabundance of glucose in blood levels.
       Noradrenalin release is also activated by nicotine because 
nicotine binds to the acetylcholine noradrenergic neuron and it 
stimulates GABA release which also incites noradrenalin release.  The 
enzyme tyrosine hydroxylase is also activated, which sensitizes the 
body to the effects of noradrenalin (Novick).  It is thought that 
continued use of nicotine possibly desensitizes the noradrenalin 
receptors, thereby increasing serotonin release, which may explain 
the sedative effects of nicotine use (Novick).  Additionally, nicotine’s 
sedative effects are explained by the activation of acetylcholine 
receptor subunit alpha4 beta2, one of five subunits, upon which 
nicotine has thirteen times the effect compared to acetylcholine 
(Novick).
       As a result of nicotine’s slightly difference chemical structure to 
acetylcholine, it has a different effect on the brain.  When nicotine 
activates cholinergic receptors of the brain it can interfere with 
normal brain functioning, unlike acetylcholine(“Mind”). See below the 
chemical differences between the two.
       
       
       Nicotine
       
       
       
       Acetylcholine
       
	 
	




Works Cited
Cholinergic Agonists.  (n.d.).  Retrieved February 19, 2005,
	from http://www.ovc.uoguelph.ca/BioMed/Courses/Public/
	Pharmacology/pharmsite/98-309/ANS/Chlinergic agonists.
	html
DiConsiglio, J.(n.d.). Nicotine. Retrieved January 24, 2005, 
	from http://www.drugabuse.gov/drugpages/nicotine.html
Extracellular Ligand-gated ion channels.  (n.d.). Retrieved
	February 19, 2005, from http://opal.msu.montana.edu/
	cftr/default.htm
Kimball, J. (n.d.). Synapses. Retrieved February 19, 2005, 
fromhttp://users.erols.com/jkinball.ma.ultranet/BiologyPages/S/Sy
napses.html
Mind Over Matter Teacher’s Guide: Nicotine. (n.d.). 
	Retrieved February 19, 2005, from http://teens.drug
	Abuse.gov/mom/tg_nic/.asp
Novick, A. (n.d.). Chemically Correct: Nicotine.  Mind and 
	Muscle Magazine.  Retrieved February 19, 2005, from
	http://www.avanlabs.com
Wikipedia. (n.d.).  Retrieved February 21, 2005, from 
	http://www.wikipedia.com

Nicotine side effects and cessation
Kiersten Kotaka
	Tobacco is the single greatest cause of disease and premature 
death in America today and is responsible for more than 430,000 
deaths each year.  There are many complications of the chronic use of 
tobacco. “Cigarette smoking is thought to cause death by aiding- if not 
causing – the development of cancer in the smoker’s body” p.236 
(Doweiko 2002). Cigarette smokers are estimated to have a 100 to 
1400% greater chance of developing some form of cancer than 
nonsmokers of the same age. (Pappas 1995)
      Associations like the American Cancer Society urge smokers and 
nicotine users to quit and provide information and advice to those 
interested in quitting nicotine. Cigarette smoking accounts for at least 
30% of all cancer deaths. It is a major cause of cancers of the lung, 
larynx (voice box), oral cavity, pharynx (throat), and esophagus, and is 
a contributing cause in the development of cancers of the bladder, 
pancreas, liver, uterine cervix, kidney, stomach, colon and rectum, and 
some leukemias. (American Cancer Society 2005) Cancers account for 
only about half of the deaths related to smoking. Smoking is also a 
major cause of heart disease, aneurysms, bronchitis, emphysema, and 
stroke, and contributes to the severity of pneumonia and asthma. 
Tobacco has a damaging affect on women's reproductive health. It is 
associated with reduced fertility and increased risk of miscarriage, 
early delivery (prematurity), stillbirth, and low birth weight in infants.  
It has also been linked to sudden infant death syndrome (SIDS 
Smoking has also been linked to a variety of other health problems, 
including cataracts, hip fractures, and peptic ulcers. (American Cancer 
Society). About 87% of lung cancer deaths are caused by smoking. 
Lung cancer is the leading cause of cancer death among both men and 
women, and is one of the most difficult cancers to treat. It is very hard 
to detect when it is in the earliest, most treatable stage.
       With all of the research and evidence of the harmful effects of 
tobacco, many people want to quit. There is an old saying “Quitting 
smoking is easy. I’ve done it a hundred times.”  The body goes through 
many changes when a person smokes, and when one quits smoking 
the body needs to repair itself after a person quits smoking. The Roy 
Castle Lung Cancer Foundation cites the following timeline for a body 
to repair after aperson quits nicotine. 20 minutes after the last 
cigarette blood pressure and pulse rate returns to normal and 
circulation improves in the hands and feet. 8 hours after stopping, 
nicotine and carbon monoxide levels in blood will be cut by half and 
oxygen levels will return to normal. Chances of heart attack start to 
fall.  24 hours after stopping Carbon Monoxide will be eliminated from 
the body and the lungs will start to clear out mucus and other smoking 
debris. 48 hours after stopping the body is free of nicotine and the 
sense of smell and taste improves. 72 hours after stopping it should be 
easier to breathe and air passages in the lungs begin to relax. Energy 
levels increase. 2 to 12 weeks after stopping, the lung function 
increases by up to 10%. Coughing, weezing and breathing problems 
lessen. 5 years after stopping the risk of a heart attack has fallen to 
about half that of a smoker. 10 years after stopping the risk of 
contracting lung cancer has fallen to half that of a smoker and your 
risk of having a heart attack is the same as if having never smoked. 
       The mind body connection needs to be considered when 
addressing nicotine addiction. A person also changes behaviors 
associated with the smoking. Smoking is a process: the forethought, 
the purchase, the lighting, and the social circle or peaceful moment 
alone.  Smoking is a ritual that incorporates breath, fire, and slow 
exhalation. Smoking becomes a habit and users often smoke when 
doing other activities like talking on the phone, driving, or drinking. 
Smoking also becomes a way to spend break times and time spent 
waiting. 
       A person is advised to think about the times when the craving to 
smoke will be strongest and remember that cravings only last three 
minutes. A person wishing to be nicotine free should examine the 
situations, social cues, and environments that they pair with smoking. 
The Roy Castle Lung Cancer Foundation identifies common situations 
that tempt people to smoke and gives alternatives because a few 
lifestyle changes can make it easier to quit smoking. For example, if a 
person wakes up and drinks coffee and smokes a cigarette, a person 
might want to try eating breakfast first, or taking a shower and then 
drink the coffee. Cars can be a tempting place for smokers, and should 
be kept smoke free. Eating and drinking are also cues for smoking. 
The temptation can be combated by taking a stroll after dinner, 
changing the type of cocktail, and telling social acquaintances about 
the desire to be smoke free. Smokers who are quitting can also reward 
themselves by saving the money that they would normally spend on 
cigarettes to spend on a vacation or something special.
       Therapists can play a role in educating clients about the process 
of quitting smoking.  Smoking cessation interventions delivered by 
professionals have increased cessation rates compared with 
interventions when no professional intervenes. It is important for a 
person who quits smoking to enlist the support of their family and 
friends. Announcing a quit date can be helpful. 
       Some people find it helpful to join a self help group to quit using 
tobacco. Nicotine Anonymous is a NonProfit 12 Step fellowship of men 
and women helping each other live nicotine-free lives. Nicotine 
Anonymous welcomes all those seeking freedom from nicotine 
addiction, including those using cessation programs and nicotine              
withdrawal aids. The primary purpose of Nicotine Anonymous is to 
help all those who would like to cease using tobacco and nicotine 
products in any form. The Fellowship offers group support and 
recovery using the 12 Steps as adapted from Alcoholics Anonymous to 
achieve abstinence from nicotine. (Nicotine Anonymous.org) Once a 
person quits smoking 2.5 to 4.5 years is added  to life expectancy. 
(Grover, Gray-Donald, Joseph and Abrahamowicz and Coupal 1994) 
Smoking is an addictive habit, but there is hope for those who can quit 
for good.
       References
American Cancer Society (2004). Smoking Information. Retrieved 
February 1, 2005, from www.americancancersociety.org
Doweiko, H. (Ed) (2002) Concepts of chemical dependency.  Pacific 
Grove: Brooks/Cole.
Grover, S.A., Gray Donald, K., Joseph, L., Abrahamowicz,M., & Coupal, 
L (1994). Life expectancy following dietary modification or smoking 
cessation. Archives of Internal Medicine, 154, 1697-1704.
Pappas,N. (1995). Secondhand smoke: Is it a hazard? Consumer 
Reports, 60, 22-24.
Roy Castle Lung Cancer Foundation. (2005). Tobacco Aids. Retrieved 
February 1, 2005 from www.roycastle.org/tobacco/aids.htm

Copyright © 2005, Dr. John M. Morgan, All rights reserved - This page last edited 02-23, 2004
If you have any feedback for the author, E-mail me